The problem of the structure of the thick filaments of vertebrate skeletal muscle is currently the subject of a number of investigations, although results thus far have been ambiguous. While the model proposed by H. E. Huxley in the 1960's has been generally discarded because it predicts too little myosin per filament, there is no decisive experiment that can choose among the models proposed in its place. In addition, none of the current models can adequately explain the placement and function of non-myosin proteins found in the thick filament at specific sites along the filament length. One way of approaching the problem of natural thick filament structure is the study of in vitro myosin aggregates, usually called synthetic thick filaments. These filaments share some of the structural periodicities of natural filaments, with the great advantage that they are much more easy to study, both structurally after aggretation and chemically during the aggregation process. In effect, this system is being used by us to analyze the structure of myosin interactions, the environmental parameters that can change these interactions, and the effects of non-myosin proteins on either the interactions or the assembly process.